This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The molecular chaperone Heat Shock Protein 90 (Hsp90) is the central player in a multi- component complex that is required for the folding and activation of numerous essential proteins including nuclear receptors and cell-cycle kinases. Very little is known about 'client' substrate protein and cochaperone interactions on Hsp90 or the structural rearrangements involved in the initial stages of chaperone activity. Previous biochemical work has shown that nuclear receptors and other clients are delivered to an Hsp90:Hop (Hsp90 organizing protein) complex by the Hsp70 chaperone.